DESCRIPTION: (Abstract from application) Discovery, confirmation and understanding of genetic determinants of longevity and frailty will require the interactive work of laboratories and human studies. We propose to begin this process by organizing a Consortium that includes laboratories dedicated to the discovery of genes that influence longevity in non- human species, studies of special human populations that are suited to discover "longevity genes," and large longitudinal studies of older adults that have phenotyping and power to confirm associations between candidate genes and longevity and frailty. The goal of the Consortium is to prepare for future collaborative studies between participants in the Consortium. To this end, we will collect genes that have been associated with longevity in non-human species and identify homologies to human genes. To expand the pool of candidate genes, we will use microarrays to identify changes in gene expression associated with aging in monkeys and humans. We will analyze date from a genomic scan for chromosomal regions associated with longevity in the population of Iceland. Members of the NIA-funded Centenarian Consortium may contribute additional candidate genes from their discovery studies. Associations between candidate genes and standardized phenotypes of longevity and frailty can be confirmed and explored in the large longitudinal human studies in the Consortium. Statistical geneticists associated with the Consortium will develop analytical methods for these studies. We will lay the groundwork for collaborations by creating a searchable database of candidate genes and their human polymorphisms; a database of measurements available in the human studies, a website to facilitate communication between Consortium members and help find information and resources relevant to research on longevity and frailty. We also will develop guidelines for sharing data and specimens and for publication of results. This Consortium will catalyze interactions between outstanding laboratory and clinical scientists that will lead to collaborative studies of the genetic determinants of longevity and frailty.